Stimulant Medications for ADHD in Autism Spectrum Disorder

Recruiting at 11 trial locations

Overseen By Samantha Sharpe

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Daniel Coury

Must not be taking: ADHD medications

Disqualifiers: Unstable medications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two common stimulant medications, methylphenidate and amphetamine, treat ADHD in children and teens with autism. Researchers aim to determine which medication works better and to understand the role of another type of ADHD medication called alpha-2 agonists (such as guanfacine and clonidine). The goal is to help doctors choose the right medication for each person, avoiding multiple trials. This trial suits children aged 4-17 years with a confirmed diagnosis of both autism and ADHD, who have not taken ADHD medication in the past week and can consistently take medication. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking your current ADHD medications at least 7 days before joining the trial. However, you can continue taking other medications like SSRIs, atypical antipsychotics, or anticonvulsants if your dose has been stable for more than 4 weeks.

What is the safety track record for these treatments?

Research has shown that medications like amphetamine and methylphenidate are generally safe for treating ADHD, though they carry some risks. Studies have found that these medications might cause more side effects than a placebo. Common side effects include trouble sleeping, loss of appetite, and a faster heartbeat.

For children with both ADHD and autism, these stimulant medications have proven effective in many cases. One study found them helpful in 69% of treatment periods, indicating that most children experienced some improvement, although side effects can still occur.

Another type of medication, called alpha-2 agonists, is also considered safe. These have been used to treat ADHD in children and can sometimes help with both ADHD and autism symptoms. Common side effects include lower blood pressure, feeling sleepy, and stomach pain.

Overall, these medications are generally well-tolerated but can have some side effects. Discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore the use of stimulant medications for managing ADHD symptoms in individuals with Autism Spectrum Disorder (ASD). Unlike the typical approach that primarily focuses on either ADHD or ASD separately, this trial looks into combining treatments like Amphetamine, Methylphenidate, and Alpha-2 Agonists to target both conditions simultaneously. This approach could potentially offer a more comprehensive management strategy, tailoring treatment to the unique needs of this population. By using a sequential, multiple assignment randomized trial (SMART) design, researchers aim to identify the most effective medication and dosage for each individual, potentially leading to more personalized and effective care options.

What evidence suggests that this trial's treatments could be effective for ADHD in autism?

In this trial, participants will be randomized to receive either Amphetamine or Methylphenidate in Stage 1. Research shows that these medications can reduce symptoms of ADHD, such as hyperactivity, difficulty paying attention, and impulsivity, in children and teens with autism. Studies have found that Methylphenidate not only helps with ADHD symptoms but may also improve some core autism symptoms. Similarly, Amphetamines significantly lessen ADHD symptoms in many patients.

In Stage 2, participants may receive an Alpha-2 Agonist or an alternate stimulant not received in Stage 1. Alpha-2 Agonists, which are not stimulants, have shown promise in managing hyperactivity and other symptoms in autism. These medications have proven more effective than a placebo (a substance with no therapeutic effect) in some cases. The evidence supports their potential use in treating ADHD in children with autism. ^{1 6 7 8 9}

Who Is on the Research Team?

Daniel Coury, MD

Principal Investigator

Nationwide Children's Hospital

Karen Kuhlthau, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 4-17 with both Autism Spectrum Disorder (ASD) and ADHD. They must be able to take medication, have a consistent caregiver, and can be on stable doses of other psychotropic meds. Excluded are those who've had multiple ADHD med trials within the last year or any safety risks.

Inclusion Criteria

Patient and/or legally authorized representative must be willing and able to give informed consent/assent for participation in this study

Patient and their caregiver must be willing and able (in the Investigator's opinion) to comply with all study requirements

Patient must have a confirmed diagnosis of ASD based on supportive evidence (e.g. referring physician's report, medical records, such as ADOS (Autism Diagnostic Observation Schedule) or CARS (Childhood Autism Rating Scale), etc.)

Exclusion Criteria

I have tried more than one ADHD medication in the last year.

I have no health issues that would make it unsafe for me to take the study medications.

Less than 4 weeks since last ADHD medication was taken

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Randomization to either Amphetamine (AMP) or Methylphenidate (MPH) based on discussion between physician and parent/caregiver

8 weeks

Bi-weekly virtual assessments

Stage 2 Treatment

Randomization to either Alpha-2 Agonist or alternate stimulant not used in Stage 1

8 weeks

Bi-weekly virtual assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpha 2 agonist
• Amphetamine
• Methylphenidate

Trial Overview

The study tests two stimulant medications—methylphenidate and amphetamine—for treating ADHD in kids with autism. It also examines alpha-2 agonists' effectiveness using a SMART design to potentially streamline medication selection for this group.

How Is the Trial Designed?

Group I: Stage 1 - Stimulant Active Control 1 Intervention

This proposed naturalistic, pragmatic clinical trial does not involve investigational drugs. Sequential, multiple assignment randomized trial (SMART) pragmatic clinical trial. Stage 1 - randomization to either Amphetamine (AMP) or Methylphenidate (MPH). The specific medication prescribed by the physician will be determined by discussion between physician and parent / caregiver and review of the subject's insurance coverage. Subjects will receive their medication from their pharmacy.

Group II: Stage 2 - Alpha-2 Agonist or Alternate Stimulant Active Control 1 Intervention

Stage 2 - randomization to either Alpha-2 Agonist or other stimulant not randomized to in Stage 1: Amphetamine (AMP) or Methylphenidate (MPH). (frequency, dosage, format, and duration dependent on participant and study doctor discussion).

Alpha 2 agonist is already approved in United States, European Union for the following indications:

Approved in United States as Guanfacine for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Hypertension

Approved in United States as Clonidine for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Hypertension

Approved in European Union as Guanfacine for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Clonidine for:

• Hypertension

Who Is Running the Clinical Trial?

Daniel Coury

Lead Sponsor

Trials

1

Recruited

500+

MaineHealth

Collaborator

Trials

76

Recruited

43,800+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

University of California, Irvine

Collaborator

Trials

580

Recruited

4,943,000+

Holland Bloorview Kids Rehabilitation Hospital

Collaborator

Trials

69

Recruited

14,100+

Published Research Related to This Trial

In a 2-year open-label study involving participants aged 6-17 with ADHD, extended-release guanfacine (GXR) demonstrated long-term safety and efficacy, with most adverse events being mild to moderate.

Significant improvements in ADHD symptoms were observed as early as the first month and continued throughout the 24-month treatment period, supporting GXR as a viable monotherapy for ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Sallee, FR., Lyne, A., Wigal, T., et al.[2013]

A study involving 226 children (174 retrospectively and 52 prospectively) found that stimulant medications like methylphenidate significantly improved symptoms of hyperactivity, impulsivity, and inattention in children with autism spectrum disorders (ASD) and ADHD, without worsening tics or repetitive behaviors.

The side effects were generally mild, with children in the ADHD-only group experiencing more nausea and headaches, while only sleep difficulties were noted in the ASD group, suggesting that stimulants can be safely used in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study. Santosh, PJ., Baird, G., Pityaratstian, N., et al.[2013]

A review of 11 studies, including 4 randomized controlled trials, suggests that psychostimulants, particularly methylphenidate, may effectively reduce ADHD-like symptoms in individuals with autism spectrum disorder.

Common side effects of psychostimulants include reduced appetite, sleep difficulties, irritability, and emotional outbursts, highlighting the need for careful monitoring and tailored treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychostimulants for ADHD-like symptoms in individuals with autism spectrum disorders. Cortese, S., Castelnau, P., Morcillo, C., et al.[2022]

Currently, the main treatments for ADHD are stimulant medications like methylphenidate and the non-stimulant atomoxetine, but there is no approved medication specifically for adults with ADHD.

Newer treatments in development, such as SPD-503 and various glutamatergic receptor agonists, aim to provide alternative mechanisms of action, potentially addressing limitations of existing therapies, including concerns about stimulant abuse and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stimulant and non-stimulant medication in current and future therapy for ADHD]. Franke, AG., Konrad, A., Lieb, K., et al.[2018]

Combining psychostimulants with new controlled-release formulations of alpha2-adrenergic agonists, like guanfacine and clonidine, can significantly enhance treatment efficacy for ADHD in children and adolescents without compromising safety.

These new formulations address previous limitations of rapid absorption and side effects, making them a promising option for patients with complex ADHD who may not respond well to monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of alpha2-adrenergic agonists in attention-deficit/hyperactivity disorder. Sallee, FR.[2022]

Methylphenidate and atomoxetine, common treatments for ADHD, can also help reduce symptoms in patients with both ADHD and autism spectrum disorders (ASD), but their effectiveness may be lower in those with ASD.

Patients with ASD may experience poorer tolerance to these medications due to the complexity of their condition, indicating a need for further controlled studies to better understand the long-term safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autism and attention deficit hyperactivity disorder: pharmacological intervention]. Fernández-Jaén, A., Martín Fernández-Mayoralas, D., Fernández-Perrone, AL., et al.[2015]

Recent research has led to the approval of several long-acting medications for pediatric ADHD, including dexmethylphenidate XR, lisdexamfetamine, and the methylphenidate transdermal system, all showing efficacy similar to traditional treatments but with extended duration of action (up to 13 hours).

Atomoxetine, the first non-stimulant ADHD treatment, has a slower onset of effect (2-8 weeks) and is less effective than stimulants, but it can benefit some children who do not respond to traditional medications, highlighting the need for diverse treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapy. May, DE., Kratochvil, CJ.[2021]

Alpha(2)-agonists like guanfacine and clonidine, originally developed for hypertension, have been effectively used for nearly 30 years to treat conditions such as ADHD and Tourette's syndrome, showing improvements in hyperactivity and inattention in children.

Guanfacine selectively targets alpha(2A)-receptors, which may enhance prefrontal function, and while both medications can cause sedation and fatigue, their effects on heart rate and blood pressure are generally modest and do not often lead to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-2 adrenergic agonists in children with inattention, hyperactivity and impulsiveness. Scahill, L.[2021]

In a study of 497 preschool-aged children treated for ADHD, α-2 adrenergic agonists (A2A) were associated with more daytime sleepiness and headaches, while stimulants led to higher rates of moodiness, sleep difficulties, and appetite suppression.

Overall, stimulants had a greater frequency of adverse effects compared to A2A medications, suggesting that the choice of treatment should consider both efficacy and the distinct side effect profiles of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study. Loe, IM., Blum, NJ., Shults, J., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10204383/

The Role of Alpha-2 Agonists for Attention Deficit Hyperactivity ...

Another study conducted in 2018 found that clonidine effectively reduced ADHD symptoms in children aged 6–12 years with comorbid tic disorders [ ...

2.

academic.oup.com

academic.oup.com/book/60743/chapter/528394653

Alpha-2 Agonists in Autism Spectrum Disorder

It has been shown to reduce hyperactivity for children and adolescents with ASD. Examples of hyperactivity can include difficulty sitting or ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39269569/

Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum ...

Results: The results demonstrated promising indications for use of alpha-2 agonists in the symptomatic management of autism spectrum disorders, including ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05916339

AWARE: Management of ADHD in Autism Spectrum Disorder

This study is a pragmatic clinical trial examining the comparative effectiveness of two stimulant medications (methylphenidate and amphetamine) in the ...

5.

canjhealthtechnol.ca

canjhealthtechnol.ca/index.php/cjht/article/download/RC1440/820?inline=1

Guanfacine for Autism Spectrum Disorder, Attention-Deficit ...

The evidence suggests that guanfacine is generally more effective than placebo to improve ADHD symptoms among those with ADHD or ASD,- but with a higher ...

6.

psychiatry-psychopharmacology.com

psychiatry-psychopharmacology.com/Content/files/sayilar/134/326-329.pdf

Use of Clonidine in Attention Deficit Hyperactivity Disorder ...

Our case report indicated that clonidine is well tolerated, safe, and effective in improving both ADHD- and ASD-related symptoms as well as ...

7.

journals.lww.com

journals.lww.com/jrnldbp/fulltext/2024/08000/attention_deficit_hyperactivity_disorder_in.12.aspx

Attention-Deficit/Hyperactivity Disorder in Medication...

For the ADHD − ASD group, stimulant medication was significantly more effective than A2As; no significant differences were found in medication effectiveness of ...

8.

psychiatryonline.org

psychiatryonline.org/doi/10.1176/appi.ajp.2015.15010055

Extended-Release Guanfacine for Hyperactivity in Children ...

Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD.

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S016372582100142X

Evidence-based pharmacological treatment options for ...

Common adverse effects include decreased appetite, sleep disturbances, increased blood pressure and pulse, headaches, irritability, and stomach pain. Moreover, ...